Investigation of patients’preferences regarding therapeutic drug monitoring of mycophenolic acid in solid organ transplantation / 中国药房

OBJECTIVE To investigate the preferences of patients who underwent solid organ transplantation regarding therapeutic drug monitoring （TDM） of mycophenolic acid （MPA） and explore the factors influencing patients’ decision-making process， so as to provide support for the development of individualized medication guidelines for MPA and improvement of clinical decision-making. METHODS The cross-sectional study was used to design the questionnaire on the patients’ preferences to accept MPA TDM， and involved patients who underwent solid organ transplantation and received MPA treatment at two tertiary hospitals in Beijing from April 14， 2022， to June 27， 2022. The Likert 5-level scoring method was used to score the patients’ preferences to accept MPA TDM， the influencing factors and their correlation of the patients’ preferences to accept MPA TDM were analyzed by Pearson correlation analysis and binary Logistic regression analysis， and the nonparametric test and chi-square test were used to rank and analyze the consistency of the factors affecting patients’ preference decision. RESULTS A total of 140 questionnaires were collected， and the effective recovery rate was 77.35%. The average preference score of 140 patients to receive MPA TDM was （4.01±0.65）， and the overall preference value was high. There were 116 （82.86%） patients agreed or strongly agreed with MPA TDM. Significant differences were observed in preference scores between patients who had previously undergone MPA TDM and those who had never undergone it （[ 4.30±0.53） scores vs. （3.80±0.65） scores， P＜0.001]. Additionally， patients’ preference scores were significantly influenced by their understanding level and attention level （P＜0.001）. The ranking of factors contributing to decision-making exhibited consistency （P＜0.001）. The factors were ranked in descending order of clinical efficacy， safety， comfortability， economy and time cost. CONCLUSIONS The patients who underwent solid organ transplantation hold high preferences towards MPA TDM. The primary factors influencing their decisions are their prior experience， understanding level， and attention level.

Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on proteomics / 中国中药杂志

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.

Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm / 中国中药杂志

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Correlation between acute intestinal toxicity and dose-volume parameters in patients with cervical cancer receiving postoperative adjuvant radiotherapy / 中华放射肿瘤学杂志

Objective:To identify dose-volume parameters to predict the incidence of acute intestinal toxicity in cervical cancer patients after postoperative adjuvant radiotherapy.Methods:Clinical data of 93 cervical cancer patients who underwent postoperative adjuvant intensity-modulated radiotherapy (IMRT) were retrospectively evaluated. The dose-volume parameters comprised the absolute volume of the bowel receiving 5-45 Gy (5 Gy interval) radiation dose and the total volume of the bowel. The acute radiation-induced intestinal toxicity was evaluated by Radiation Therapy Oncology Group (RTOG) criteria. The association between the irradiated bowel volume and acute intestinal toxicity was analyzed.Results:A total of 26 (28%) patients experienced grade ≥2 acute intestinal toxicity. A strong relationship between grade ≥2 acute intestinal toxicity and the irradiated small bowel volume was observed at the total volume of small bowel, small bowel V 5 Gy, V 10 Gy and V 15 Gy (all P<0.05). Small bowel V 10 Gy ( HR=1.028, 95% CI, 0.993-1.062, P=0.029) and small bowel ?V 15 Gy( HR=0.991, 95% CI, 0.969-1.013, P=0.034)were the independent risk factors for evident acute intestinal toxicity. Conclusion:Dose-volume parameters of the small bowel can be used as predictors for the occurrence of grade ≥2 acute intestinal toxicity in cervical cancer patients undergoing postoperative adjuvant radiotherapy.

An anatomical study of the external bone graft axis from the pedicle to the endplate from T10 to L5 in compression healing fractures of the anterior vertebral column / 中华创伤骨科杂志

Objective:To anatomically study the external bone graft axis from the pedicle (canal) to the endplate designed for compression healing fractures of the anterior vertebral column in freshly dried vertebral specimens from T10 to L5.Methods:Eight groups of freshly dried vertebral specimens from T10 to L5 (128 vertebral bodies and 256 lateral pedicles and lateral vertebral bodies) were used to observe the vertebral axis of the pedicle (canal), the internal sagittal diameter of the pedicle (canal), and the sagittal diameter of the vertebral body, and the position of vertebral pedicle (canal) axis (f-angle) before design of the external bone graft axis from the pedicle (canal) to the endplate of the compression healing vertebral body. (1) The internal sagittal diameter of the pedicle (canal) was divided into 3 segments. The lateral segment of the vertebral plate was wide, the middle segment of the isthmus of the vertebral arch was narrow and the medial segment of the terminal segment of the vertebral arch was wide. The narrow isthmus of the middle arch (canal) was used as a transposition axis in the design of the axis of the bone graft from the vertebral arch (canal) to the endplate of the compression healing vertebral body. (2) The axis of the vertebral body of the pedicle (canal) was located medial to the transposition axis, parallel to the f-angle at 0° as described by Saillant G. (3) The compression degree of the vertebral body was measured at the outer edge of the lateral anterior column, with Ⅰ° for less than 1/4 compression of the anterior column of the vertebral body, Ⅱ° for 1/4 to 2/4, Ⅲ° for 2/4 to 3/4 and Ⅳ° for more than 3/4 of the compression. (4) The f-angle described by Salliant G at the entry end which was corresponding to the endplate of the compression healing vertebral body was used to design the pedicle (canal) to the outer implant axis of the endplate of the compression healing vertebral body.Results:At an f-angle of 8° to 10°, the bone graft axis was aligned with the Ⅱ° compression healing vertebral endplate on the superior endplate side of the vertebral body axis of the arch; at an f-angle of 16° to 18°, the bone graft axis corresponded to the superior endplate of the Ⅰ° compression healing vertebral body. At an f-angle of -10°~-8°, the bone graft axis corresponded to the Ⅲ° compression healing vertebral endplate on the inferior endplate side of the vertebral body axis of the arch; at an f-angle of -18°~-16°, the bone graft axis corresponded to the inferior endplate of the Ⅳ° compression healing vertebral body.Conclusions:The external axis from the pedicle (canal) to the endplate designed in the present anatomic study for compression healing fractures of the anterior vertebral column allows for safe and easy granular bone implantation due to the toughness of the cortical bone around the arch root (canal) in addition to the precise design of the bone graft axis from the pedicle to the endplate from T10 to L5.

Recent advances in efficacy and safety evaluation of adalimumab in non-infectious uveitis / 中华实验眼科杂志

Non-infectious uveitis (NIU) is a serious sight-threatening disease caused by chronic inflammation and its complications.First-line treatment of NIU consists of topical and/or systemic corticosteroids and/or immunosuppressive drugs.Tumor necrosis factor-α inhibitors are recommended in cases of ineffectiveness or intolerance to conventional treatment of NIU.Adalimumab is a fully human monoclonal antibody that is widely used in the treatment of uveitis.Adalimumab is very effective in the treatment of NIU in several prospective and retrospective studies.Adalimumab has also been shown to be safe and effective in the treatment of NIU associated with various systemic diseases in many studies.The application of adalimumab in children, pregnant women, lactating women and other special populations has shown clear efficacy and acceptable side effects.The long-term safety of adalimumab is relatively stable, and no new adverse events have been reported.Compared with other tumor necrosis factor-α inhibitors, adalimumab also has a clear efficacy and better tolerability.This article reviewed the efficacy and safety of adalimumab in the treatment of NIU.

Risk assessment and influencing factors of malnutrition among community-dwelling older adults in Minhang District of Shanghai / 环境与职业医学

Background The prevalence of malnutrition in older adults is high. Early use of appropriate screening scales for malnutrition risk and early intervention can effectively improve life quality of the elderly in communities. Objective To evaluate the risk of malnutrition among the community-dwelling elderly in a district of Shanghai and explore its influencing factors. Methods From October to December 2021, a total of 960 seniors aged 65 years and above in community committees (villages) of Minhang District were selected by stratified random sampling. Trained investigators conducted one-to-one interviews with included seniors using questionnaires. The questionnaires included the Geriatric Depression Scale (GDS), the Activity of Daily Living Scale (ADL), and the malnutrition risk assessment for elderly adults. Height, weight, waist circumference, and calf circumference were measured. Chi-square test and logistic regression were used to analyze potential influencing factors of malnutrition in the elderly. Results Among the 960 community-dwelling seniors of Minhang District, 13 (1.35%) were malnourished and 311 (32.40%) were at the risk of malnutrition. There were statistically significant differences in nutritional status across different categories of age, sex, monthly family income, education level, marital status, waist circumference, dental health status, activity of daily living, nutrition knowledge, suffering from chronic diseases, having > 3 chronic diseases, taking > 3 long-term prescriptions, depression symptoms, sleeping duration, daily outdoor activity time, number of daily food species (milk/soy products/fish/meat/poultry/eggs), daily intake of vegetables and fruits, daily consumption of cooking oil, frequency of physical exercise, frequency of smoking, and living alone (P < 0.05). The logistic regression analysis results showed that poor dental conditions, insufficient daily intake of milk/soy products/fish/meat/poultry/eggs (<3 kinds), insufficient daily intake of vegetables and fruits (<500 g), excessive daily consumption of cooking oil (>25 g), insufficient daily outdoor activities (<1 h·d−1), living alone, low educational level (primary school and below), suffering from chronic diseases, having > 3 chronic diseases, taking > 3 long-term prescriptions, and being single/widowed/divorced were the main risk factors for nutritional abnormalities in the elderly (P< 0.05). Conclusion The elderly in Minhang District of Shanghai have a high malnutrition risk, and their nutritional status is affected by multiple factors, including poor dental status, irrational dietary structure, insufficient time for outdoor activities, suffering from chronic diseases, having > 3 chronic diseases, taking > 3 long-term prescriptions, low educational level, living alone, and being single/widowed/divorced.

Effect of chemogenetic manipulation of PVN corticotropin-releasing factor-expressing neurons on excitability of presympathetic neurons in SHR / 中国药理学通报

Aim To observe the effect of corticotropin-releasing factor ( CRF) -expressing neurons on presympathetic neurons in hypothalamic paraventricular nucleus ( PVN) of normotensive Wistar Kyoto ( WKY) rats or spontaneously hypertensive rats (SHR) , and to elucidate the underlying neuronal circuit mechanism of central sympathetic hyperexcitability. Methods The expression levels of CRF protein in WKY rats and SHR PVN were determined by Western blot. Meanwhile, the WKY and SHR PVN CRF-expressing neurons and presympathetic neurons were observed by immunofluo-rescent staining. Adult WKY rats and SHR were used in this study. By microinjection of Cre-dependent ade-no-associated viruses ( AAV) that specifically recognized the CRF promoter and AAV of chemogenetics into the PVN, CRF-expressing neurons expressed designer receptors exclusively activated by designer drugs (DREADDs). Human M3 muscarinic DREADD coupled to Gq receptor ( hM3 Dq) was specifically expressed in PVN CRF-expressing neurons in WKY rats, while human M4 muscarinic DREADD coupled to Gi receptor ( hM4Di) was specifically expressed in PVN CRF-expressing neurons in SHR. Clozapine-N-oxide (CNO) , as a designer ligand, would couple to excitatory hM3Dq or inhibitory hM4Di to regulate the excitability of PVN CRF-expressing neurons. Then the PVN presympathetic neurons were retrogradely labeled by microinjection of fluosecent tracer into the intermedio-lateral column (IML) of spinal cord. Lastly, whole cell patch clamp was used to determine the effect of CNO (10 jjumol L~ ) on spontaneous excitatory postsynaptic currents ( sEPSCs) and current-evoked firing of PVN presympathtic neurons of WKY rats and SHR. Results The expression of CRF protein in the PVN of SHR was significantly higher than that of WKY rats, and the activity and number of CRF-expressing neurons in the PVN of SHR were increased. PVN CRF-expressing neurons were expressed with chemogenetic DREADDs and PVN presympathetic neurons were retrogradely labeled with fluorescent tracer in WKY rats and SHR. In SHR expressed with chemogenetic inhibitory hM4Di-mCherry of PVN CRF-expressing neurons, bath application of CNO to the brain slices resulted in a significant decrease in sEPSCs frequency, but no change in their amplitude of labeled PVN presympathetic neurons. In contrast, in WKY rats expressed with excitatory hM3Dq-eGFP of PVN CRF-expressing neurons, CNO had no obvious effect on the sEPSCs frequency and amplitude in PVN presympathetic neurons. Furthermore, bath application of CNO had no significant effect on current-evoked firing of PVN presympathetic neurons of either WKY rats with hM3Dq-eGFP expression in CRF neurons or SHR with hM4Di-mCherry expression in CRF neurons. Conclusions The activity and number of PVN CRF-expressing neurons are increased in SHR, and CRF-expressing neurons enhance the excitability of presympathetic neurons, which acts as a regulatory neuronal microcircuit between CRF neurons and presympathetic neurons in the PVN.

Endogenous corticotropin-releasing factor potentiates the excitability of presympathetic neurons in paraventricular nucleus via activation of its receptor 1 in spontaneously hypertensive rats / 生理学报

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.

Effect of post-rewarming fever after targeted temperature management in cardiac arrest patients: a systematic review and meta-analysis / 世界急诊医学杂志（英文）

@#BACKGROUND: Targeted temperature management (TTM), as a therapeutic temperature control strategy for cardiac arrest (CA), is recommended by guidelines. However, the relationship between post-rewarming fever (PRF) and the prognosis of CA patients is unclear. Therefore, we aim to summarize the studies regarding the influence of PRF on patients with CA. METHODS: EMBASE, PubMed, and Cochrane Central databases were searched from inception to March 13, 2022. Randomized clinical trials (RCTs) and cohort studies on PRF in CA patients were included. According to the heterogeneity, the meta-analysis was performed using a random effects model or fixed effects model to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The outcome data were unfavorable neurological outcome and mortality. RESULTS: The meta-analysis included 11 observational studies involving 3,246 patients. The results of the meta-analysis show that PRF (body temperature >38.0 °C) has no effect on the neurological outcome of CA patients (OR 0.71, 95% CI 0.43-1.17, I2 82%) and has a significant relationship with lower mortality (OR 0.63; 95% CI 0.49-0.80, I2 39%). However, PRF with a stricter definition (body temperature >38.5 °C ) was associated with worse neurological outcome (OR 1.44, 95% CI 1.08-1.92, I2 45%) and higher mortality (OR 1.71, 95% CI 1.25-2.35, I2 47%). CONCLUSION: This study suggests that PRF >38.0 °C may not affect the neurological outcome and have a lower mortality in CA patients who completed TTM. However, PRF >38.5 °C is a potential prognostic factor for worse outcomes in CA patients.

Epidemiological distribution of genotypes and sub-genotypes of hepatitis B virus in 15 ethnic groups in China / 中华流行病学杂志

Objective: To understand the distribution of genotypes and sub-genotypes of HBV in different ethnic groups in China. Methods: The HBsAg positive samples were selected by stratified multi-stage cluster sampling from the sample base of national HBV sero-epidemiological survey in 2020 for the amplification of S gene of HBV by nested PCR. A phylogeny tree was constructed to determine the genotypes and sub-genotypes of HBV. The distribution of genotypes and sub-genotypes of HBV were analyzed comprehensively by using laboratory data and demographic data. Results: A total of 1 539 positive samples from 15 ethnic groups were successfully amplified and analyzed, and 5 genotypes (B, C, D, I and C/D) were detected. The proportion of genotype B was higher in ethnic group of Han (74.52%, 623/836), Zhuang (49.28%, 34/69), Yi (53.19%, 25/47), Miao (94.12%, 32/34), Buyi (81.48%, 22/27). The proportions of genotype C were higher in ethnic groups of Yao (70.91%, 39/55). Genotype D was the predominant genotype in Uygur (83.78%, 31/37). Genotype C/D were detected in Tibetan (92.35%,326/353). In this study, 11 cases of genotype I were detected, 8 of which were distributed in Zhuang nationality. Except for Tibetan, sub-genotype B2 accounted for more than 80.00% in genotype B in all ethnic groups. The proportions of sub-genotype C2 were higher in 8 ethnic groups, i.e. Han, Tibetan, Yi, Uygur, Mongolian, Manchu, Hui and Miao. The proportions of sub-genotype C5 were higher in ethnic groups of Zhuang (55.56%, 15/27) and Yao (84.62%, 33/39). For genotype D, sub-genotype D3 was detected in Yi ethnic group and sub-genotype D1 was detected in both Uygur and Kazak. The proportions of sub-genotype C/D1 and C/D2 in Tibetan were 43.06% (152/353) and 49.29% (174/353). For all the 11 cases of genotype I infection, only sub-genotype I1 was detected. Conclusions: Five genotypes and 15 sub-genotypes of HBV were found in 15 ethnic groups. There were significant differences in the distribution of genotypes and sub-genotypes of HBV among different ethnic groups.

Screening novel inhibitors of squalene epoxidase and their effects on hepatocellular carcinoma / 药学学报

Squalene epoxidase (SQLE) is a potential target for the treatment of liver cancer. Bioinformatics analysis indicated that the high expression of SQLE was closely related to the clinical stage and poor prognosis of patients with liver cancer. However, the existing inhibitors against SQLE 195 tyrosine residue (Y195) cannot be used clinically due to severe side effects. In this study, 35 small-molecule compounds targeting SQLE 335 tyrosine residue (Y335) were selected by computer virtual screening. Combined with MTT assay, 3 candidate compounds (19#, 31# and 35#) with significant inhibitory effects on the proliferation of Huh7 cell line were obtained. Further studies showed that these 3 compounds could inhibit the migration of Huh7 cells, reduce the contents of total and free cholesterol, up-regulate the expression of tumor suppressor gene PTEN, and down-regulate the expression of PI3K and AKT proteins. The results showed that the novel inhibitors 19#, 31# and 35# targeting SQLE Y335 could reduce cholesterol content, inhibit the proliferation and migration of Huh7, thus playing an anti-liver cancer role.

Flavonoid glycosides from the water extract of Artemisia annua L / 药学学报

Twenty one flavonoid glycosides were isolated and purified from n-butanol portion of the water extract of A. annua by various chromatographic techniques such as HP-20 macroporous adsorption resin, silica gel, ODS, Sephadex LH-20 gel column chromatography and preparative high performance liquid chromatography. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as axillarin-7-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside (1), orientin (2), apigenin-6-C-β-D-glucopyranosyl-8-C-β-L-arabinopyranoside (3), apigenin-6-C-β-D-galactopyranosyl-8-C-β-L-arabinopyranoside (4), apigenin-6-C-β-L-arabinopyranosyl-8-C-β-D-glucopyranoside (5), apigenin-6-C-α-L-arabinofuranosyl-8-C-β-D-glucopyranoside (6), quercetin-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside (7), apigenin-6-C-α-L-arabinopyranosyl-8-C-β-D-glucopyranoside (8), vicenin-2 (9), patuletin-7-O-β-D-glucopyranoside (10), luteolin-6-C-glucopyranoside (11), vitexin (12), kaempferol-3-O-β-galactopyranosyl-(1→2)-β-glucopyranoside (13), quercetin-7-O-β-D-glucopyranoside (14), patuletin-3-O-β-D-glucopyranoside (15), 7-O-methyl-quercetagetin-6-O-β-D-glucopyranoside (16), quercetin-3-O-β-D-glucopyranoside (17), nepitrin (18), rutin (19), kaempferol-3-O-β-sophoroside (20), and patuletin-3-O-rutinoside (21). Compound 1 is a new compound, compounds 2, 4, 6, 7, 10, 11, 13, 15, 16, 18, 20 and 21 are isolated from A. annua for the first time. In the anti-inflammatory assay, compound 1 inhibited the release of IL-6 from LPS-induced RAW264.7 cells to significantly degrees with the high (100 μmol·L-1), medium (50 μmol·L-1), low (25 μmol·L-1) concentration.

Baicalin Alleviates LPS-Induced Acute Lung Injury in Rats Through p38 MAPK/NLRP3 Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects and mechanism of baicalin （BA） on lipopolysaccharide （LPS）-induced acute lung injury in rats. MethodEighty healthy male SD rats were randomly divided into the control group， model group， low-dose BA （BA-L） group， medium-dose BA （BA-M） group， high-dose BA （BA-H） group， dexamethasone （DEX） group， SB203580 group， and BA + SB203580 group， with 10 rats in each group. The rats in the BA-L， BA-M， and BA-H groups were injected intraperitoneally with different doses （10， 50， 100 mg·kg-1） of BA solution， the ones in the DEX group with 5 mg·kg-1 DEX solution， the ones in the SB203580 group with 0.5 mg·kg-1 SB203580 solution， the ones in the BA + SB203580 group with 100 mg·kg-1 BA solution and 0.5 mg·kg-1 SB203580， and those in both the control group and model group with the same volume of normal saline， once per day， for seven successive days. One hour after the last administration， rats in all groups except for the control group were given 5 mg·kg-1 LPS via intratracheal instillation for inducing the acute lung injury， whereas those in the control group received the same volume of normal saline solution. Twelve hours later， the lung tissues were sampled and stained with htoxylin-eosin （HE） for observing the pathological changes， followed by the counting of the total number of cells and neutrophils in bronchoalveolar lavage fluid （BALF）. The wet/dry weight ratio of the lung tissue and the contents of serum superoxide dismutase （SOD） and malondialdehyde （MDA） were measured. The activity of reactive oxygen species （ROS） in the lung tissue was detected by immunofluorescence and the levels of interleukin-1β （IL-1β）， interleukin-18 （IL-18）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in BALF by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was conducted to determine the relative expression of p-p38 mitogen-activated protein kinase （MAPK） and Western blotting was carried out to detect the protein expression levels of p-p38 MAPK， thioredoxin interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3）， and cysteinyl aspartate specific protease-1 （Caspase-1） in the lung tissue. ResultCompared with the control group， the model group displayed inflammatory pathological changes in lung tissue， elevated wet/dry weight ratio， total number of cells and neutrophils in BALF， and ROS and MDA levels （P<0.01）， decreased SOD activity （P<0.01）， and up-regulated IL-1， IL-18， IL-6， TNF-α， p-p38 MAPK， NLRP3， and Caspase-1 expression （P<0.01）. Compared with the model group， BA at different doses， SB203580， and BA + SB203580 all effectively alleviated the pathological changes in lung tissue induced by LPS， reduce the lung wet/dry weight ratio， the total number of cells and neutrophils in BALF， and ROS and MDA levels （P<0.05，P<0.01）， enhanced the activity of SOD （P<0.05，P<0.01）， and down-regulated the expression of IL-1β， IL-18， IL-6，TNF-α， p-p38 MAPK， NLRP3， and Caspase-1 in lung tissue （P<0.05，P<0.01）. ConclusionBA has a protective effect against LPS-induced acute lung injury， which may be related to its inhibition of p38MAPK/NLRP3 signaling pathway and the improvement of inflammatory response.

Herbal Textual Research on Platycodonis Radix in Famous Classical Formulas / 中国实验方剂学杂志

In this paper， the name， origin， quality evaluation， producing area and processing methods of Platycodonis Radix used in the famous classical formulas are researched by consulting related materia medicas， prescription books and medical books of the past dynasties. It was found that Platycodonis Radix was the correct name in the materia medicas of the past dynasties， which was named for its "roots are strong but the stems are straight". Its dominant base of the past dynasties was Platycodon grandiflorus， and since the Ming and Qing dynasties， Hexian county of Anhui has been respected as the representative authentic producing area. In modern times， it has been concluded that the quality of Platycodonis Radix is best if the body is dry， thick and uniform， solid， white in color， and bitter in taste. In ancient times， the processing methods of Platycodonis Radix were mainly removing the reed head and floating skin， rice simmering and drying， and slicing and micro-frying. In modern times， its processing methods have been mainly simplified to peeling and cutting into thick slices. Therefore， it is recommended to use the dry roots of P. grandiflorus and its raw products in the famous classical formulas.

Application of blood routine and four inflammatory markers in children with lower respiratory tract infection / 中华检验医学杂志

Objective:To evaluate the differential expression of blood routine in different types of infection and the diagnostic value of C-reactive protein (CRP), procalcitonin (PT), ferritin (SF) and lactate dehydrogenase (LDH) in bacterial and mycoplasma pneumonia and their early warning value in severe cases.Method:A total of 627 patients, including 176 cases of bacterial pneumonia, 275 cases of mycoplasma pneumonia, 176 cases of viral infection and 180 cases of normal control were collected from May 2018 to December 2019 in children′s Hospital Affiliated to Capital Institute of Pediatrics. The mycoplasma pneumonia group was divided into mild group (151 cases) and severe group (124 cases) according to the results of lavage fluid RNA-examination. All patients received completed blood routine test at the first day of admission, patients in bacteria group and Mycoplasma group received the examination of four inflammatory indicators. The Kruskal-Wallis test was used to analyze the differences in blood routine results between different infection groups, and the differences of inflammatory indexes between bacterial group and Mycoplasma mild and severe group. The receiver operating characteristic (ROC)-curve method was used to analyze the predictive value of inflammatory indexes between different infection groups.Results:There were significant differences in leukocyte count, neutrophil, lymphocyte and monocyte percentage between bacterial pneumonia, mycoplasma pneumonia, viral infection and normal control group ( P<0.05). The differences of four inflammatory indexes in bacterial group, mild Mycoplasma group and severe group were statistically significant ( P<0.05). The rest of the index (CRP, PCT, LDH, SF and white blood cell count) were P<0.05 (CRP: area under curve [AUC] 0.799; PCT: AUC 0.579; LDH: AUC 0.651; SF: AUC 0.854), in mild and severe mycoplasma group, except WBC, by ROC-curves analysis. The AUC value of the area under the curve of CRP and SF is high, and the sensitivity and specificity at the diagnostic critical point are high, which has great diagnostic value (CRP: diagnostic critical point 12.55 mg/L, sensitivity 0.719, specificity 0.755; SF: diagnostic critical point 176.02 μg/L, sensitivity 0.765, specificity 0.960). ROC curve results also showed that of PCT, White blood cell and neutrophil percentage had the diagnostic value in bacterial infection and mycoplasma infection, P<0.05 (PCT: AUC 0.658; leukocyte: AUC 0.804; neutrophil: AUC 0.630). Leukocyte count is the best differential index (diagnostic critical point 9.585×10 9/L, sensitivity 0.778, specificity 0.698), PCT has higher sensitivity at the diagnostic critical point of 0.55 μg/L, but the specificity is slightly lower (diagnostic critical point of 0.55 μg/L, sensitivity 0.862, specificity 0.366). Conclusions:PCT and leukocyte count can be used as the preferred inflammatory indexes to distinguish bacterial and mycoplasma infection. CRP, LDH, PCT and SF can be used as early warning indexes to evaluate severe mycoplasma infection.

Ultrasmall nanoprobe in MR/CT bimodal imaging for tumor angiogenesis / 中华核医学与分子影像杂志

Objective:To fabricate tAu@glutathione(GSH)@Gd nanoprobe for tumor angiogenesis bimodal (MR/CT) imaging, and evaluate its characteristics and potential for MR/CT imaging in vivo. Methods:The tAu@GSH@Gd nanoprobes were constructed by encapsulating Au and Gd atoms into the GSH shell with cyclic asparagine-glycine-arginine (cNGR) peptide conjugation. EMT-6 BALB/c mice subcutaneous transplantation tumor models were established ( n=30) and divided into blank control group (saline), control group (Au@GSH@Gd nanoparticles) and experimental group (tAu@GSH@Gd nanoprobes) ( n=10 in each group). In vivo MR/CT imaging and distribution study were performed at different time points after tail intravenously injection. Relative MR signal value and relative CT value of tumor site and main organs in mice were used to evaluate MR/CT imaging property and biological distribution. After that, tumor tissues were collected for silver staining to study the accumulation of Au@GSH@Gd nanoparticles and tAu@GSH@Gd nanoprobes. Independent-sample t test was used for data analysis. Results:The tAu@GSH@Gd nanoprobes were (6.40±0.22) nm with high T 1 relaxation efficiency ((36.91±0.07) mmol·L -1·s -1). MR/CT imaging of tAu@GSH@Gd nanoprobes showed good performance in vitro. In vivo MR/CT imaging demonstrated MR/CT imaging of tumor was significantly enhanced by tAu@GSH@Gd nanoprobes after 2 h post injection. The strongest enhancement was observed at 24 h, with an increased relative MR signal value from 1.04±0.12 (before injection) to 1.84±0.26 ( t=12.61, P=0.006), and increased relative CT value from 1.01±0.04 (before injection) to 1.95±0.05 ( t=15.34, P=0.004). The highest MR/CT effect in control group appeared at 16 h, with the relative MR signal value of 1.50±0.06 and the relative CT value of 1.53±0.10, which were significantly lower than those in experimental group (1.84±0.26 and 1.95±0.05; t values: 5.35 and 16.46, both P<0.05). Distribution in normal tissues showed that most of tAu@GSH@Gd nanoprobes were metabolized through the kidneys. Tissue silver staining experiment verified the tumor angiogenesis targeting effect. Conclusion:The tAu@GSH@Gd nanoprobes exhibit favorable tumor angiogenesis target MR/CT imaging ability, providing a new design concept and basis for assessing tumor angiogenesis.

Research progress in the application of polydopamine multifunctional nanocontrast agents in molecular imaging of tumors / 国际生物医学工程杂志

The development of multifunctional nanocontrast agents with high sensitivity, high specificity, and low toxicity so that they can precisely localize tumors and reflect tumor biological information in real time is the core of promoting the development of tumor molecular imaging technology and realizing early and precise tumor diagnosis. Polydopamine (PDA) nanomaterials are bionanomaterials with a structure extremely similar to that of natural melanin. They can be easily fabricated and functionalized, and can achieve controlled assembly of functional molecules such as contrast components and targeting ligands via metal coordination, π-π stacking, electrostatic adsorption, and other methods. They have good biocompatibility and biodegradability, show great potential for clinical translation, and have been widely used in molecular imaging of tumors. In this review paper, the preclinical studies of PDA nanoparticles are reviewed as well as the synthesis methods, functionalized modification, and assembly strategies of PDA nanoparticles and their applications in tumor molecular imaging. The development trends of PDA are also presented to promote their application in the field of tumor molecular imaging.

Recovery of IFN-7-secreting T and NK cells after low dose X-ray radiation injury and the protective effect of Prepared Radix Rehmanniae / 中国药理学通报

Aim To investigate the reeovery of I FN-7- tion and the protective effect of Prepared Radix Reh- secreting T and NK cells after low dose X-ray irradia- manniae ( PRR ).Methods X-ray 2.5Gy was used to establish a mouse irradiated model,and some irradiated mice were used to establish a melanoma lung cancer metastasis model or to be treated by PRR.The propor¬tion and number of Tel , Thl and NK1 cells with the phenotypes of IL-12R and IL-15R were detected by flow cytometry.The transcription levels of IL-12,1L- 15 ,STAT4 and T-bet were detected by RT-qPCR.Re¬sults Within four days after irradiation,Thl ,Tcl and NK1 cells were significantly reduced ( P < 0.05 , P < 0.01).The expression of IL-12R and IL-15R de¬creased in Thl and Tel cells , and increased in NK1 cells ( P < 0.05 ).On day 8 of irradiation , NK1 and Tc 1 cells recovered or exceeded basic level, but Th 1 was still lower than normal level ( P < 0.05 ) , and tumor load of irradiated mice increased significantly (P <0.01).Compared with radiation group, the propor¬tion and absolute numbers of NK1 ,Tel and Thl were up-regulated by PRR (P <0.05 <0.01) ,and tumor load was down-regulated ( P < 0.05 ).Conclusions The impaired reconstitution of Thl cells after irradia¬tion affects the anti-tumor ability.PRR promotes the recover}' of IFN-∗y-secreting T and NK cells after radia¬tion and reduces the risk of tumor metastasis in mice.

Arthroscopic, histological and imaging studies of rare abnormal insertion points in the anterior root of the medial meniscus / 中华骨科杂志

Objective:To investigate the characteristics of an abnormal attachment point of the anterior horn of the medial meniscus (AHMM) by methods of arthroscopy, radiological imaging, and pathology.Methods:A total of seven cases of a rare abnormal attachment (anteromedial meniscofemoral ligament, AML) connecting the AHMM and anterior cruciate ligament (ACL) were identified in the more than six thousand arthroscopic procedures from January 2018 to April 2021. During the procedures, subtotal meniscal resection or meniscal repair was performed in all cases. Tissue removed intraoperatively was used for pathologic examination. For this study, the preoperative MRI films of these patients were retrospectively examined.Results:Finally, seven cases with diagnosed meniscal tears were included in this study, including 4 males and 3 females with a mean age of 37.85±7.70 years (range, 27-50 years). The AML, which extends outward and upward and is anterior to the ACL, begins at the AHMM and ends anterior to the femoral attachment of the ACL. The histological staining showed that the AML was a bundle of collagen fibers, whereas the ACL was a bundle of dense fibrous collagen. The AML could be clearly identified in the proton-weighted image of sagittal MRI preoperatively and showed a low signaling similar to the signal intensity of the ACL. AML was easily identified on sagittal MRI but not on axial and coronal MRI. In three patients who underwent bilateral MRI, the AML structure was found in both knees.Conclusion:The incidence of rare anatomic variation between the AHMM and the lateral condyle of the femur is 0.1%, usually occurring in both knees simultaneously. In cases with this variation, there is no bony attachment in the AHMM connected to the ACL via the AML. After transection of the AML, the annular fibrous structure and mechanical properties of the meniscus are damaged, as consequently the AML should be carefully protected in clinical practice.